The principal aim of this proposal is to determine the nature of organ blood flows and vascular resistances, and the role of the sympathetic vasomotor nervous system on the total organ and regional circulations in the development of hypertension. These studies will emphasize adrenergic function and vascular responsiveness. In order to achieve this objective, regional and organ vascular resistances will be determined in the spontaneously hypertensive rat of Okamoto and Aoki (SHR) during stimulation or inhibition on sympathetic nerves, during adrenergic vascular receptor stimulation or inhibition, or after chronic pharmacologic treatment. Vascular resistance in all organs will be determined from the arterial pressure and respective organ blood flow rate; and organ flow will be calculated from cardiac output and its organ distribution. Cardiac output and its distribution will be measured in conscious intact rats by the Fick procedure and radioactive microsphere technique, respectively. The results of these studies will determine whether: the vascular resistance in SHR is uniformly elevated; the sympathetic nervous system exerts an abnormal influence on the vasculature; specific organ vasculatures have abnormal responsiveness to catecholamines; and intrinsic vascular tone is altered in hypertension. Of great practical significance will be the knowledge gained concerning the extent to which antihypertensive therapy alters specific organ hemodynamics. Since these studies will be conducted in the conscious rat, treated acutely or in a prolonged fashion with antihypertensive compounds, the results will provide a more rational basis for interpretation of more highly controlled in vitro and in situ studies of sympathetic functions in hypertension and a more comprehensive understanding of the pathophysiological circulatory alterations in hypertension and the responses to antihypertensive therapy. BIBLIOGRAPHIC REFERENCES: G.M. Walsh, M. Tsuchiya, and E.D. Frohlich. Direct Fick Application for Measurement of Cardiac Output in Rat. J. Appl. Physiol. 40:849-853, 1976. G.M. Walsh and A.J. Tobia: Altered Autoregulatory Function of the Subclavian Vascular Bed in Young Spontaneously Hypertensive Rats (SHR). Fed. Proceed. 33:583, 1975.